Serotonin 5-HT1A receptors are implicated in Alzheimers disease, dementia, anxiety, schizophrenia, and depression, and significant efforts have been undertaken to develop various compounds that bind to these receptors for potential use in diagnosis and therapy of disorders associated with serotonin 5-HT1A receptors. Among other proposed approaches, particularly desirable compounds include those suitable for selective positron emission tomography (PET) analysis.
Currently known serotonin 5-HT1A receptor ligands for animal and human diagnostic imaging studies include 11C-WAY-100635 (WAY), 18F-FCWAY and 18F-MPPF. Other known compounds include those in Prior Art FIG. 1 in which (1) is WAY-100635, (2) is CPC-222, (3) is SWAY, and (4) is JWAY. Still further known ligands (which may or may not be labeled) are described in Nuclear Biology and Medicine (2000) Vol. 27, 441-447, in WO96/01656 and WO94/19026, and in U.S. Pat. Nos. 6,861,427, 6,831,084, 6,821,981, and 6,670,400. While such compounds target the serotonin 5-HT1A receptors to at least some degree, numerous difficulties nevertheless exist. Among other problems, all or almost all of the known compounds are metabolized at a relatively fast rate, and/or are eliminated from plasma in an undesirably short time. Thus, data analysis is often difficult. Still further, the synthesis of such compounds is frequently difficult to achieve in adequate yields. Moreover, where 18F is used as a radiolabel, compounds are often rendered chemically instable. Worse yet, affinity of 18F-labeled compounds to the target receptor are typically relatively low.
Thus, while numerous compositions and methods for serotonin 5-HT1A receptor ligands are known in the art, all or almost all of them suffer from one or more disadvantages. Therefore, there is still a need to provide improved compositions and methods for such ligands, especially for 18F-labeled ligands.